In the field of medicine, there is a constant demand for new and improved biological markers (biomarkers) for diagnosing or prognosticating pathological conditions and for evaluating the efficacy of a treatment being applied. In general terms, the concentration of a biomarker from a patient sample is by statistical association taken as indication for the presence of, the severity of, or the risk for a pathological condition. One widely studied subset of biomarkers is peptides in biological fluids, such as blood, cerebrospinal fluid or urine. The number of different peptides present in the biological sample may vary from tens to tens of thousands, depending on the method of analysis and the type of sample. It is thus clear than many medically relevant peptide biomarkers are yet to be discovered.
A human protein named complement C3 is a well-studied component of the innate immune system, and substantial amounts of complement C3 circulate in the blood. The classical complement pathway typically requires antigen:antibody complexes for activation (specific immune response), whereas the alternative and mannose-binding lectin pathways can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response). In all three pathways, a C3-convertase cleaves and activates component C3, generating C3a and C3b, and causing a cascade of further cleavage and activation events.
A number of complement C3 peptide fragments useful as biomarkers are known in the literature. For instance, WO/2004/079371 discloses peptide fragments of complement C3 as markers useful in the diagnosis of autism. As another example, US20050048584A1 discloses a method for detecting Alzheimer's disease and differentiating Alzheimer's disease from other demential diseases using peptide biomarkers originating from complement C3.
Autism is a neuropsychiatric disorder with varying degrees of severity which affects around 2-5 in 1000 children worldwide and perhaps up to 1:110 in the US. The aetiology of autism is not understood but it is thought that both genetic and environmental factors contribute. Diagnosis for autism requires expert evaluation of the child's behaviour and given the enormous implications of a diagnosis to the child and the family, setting a firm diagnosis often takes significant time and effort. As such, a clinical assay based on objective measurements of biological variables for diagnosing autism is in great demand.
Treatment of autism includes behavioural training and management using positive reinforcement, self-help, and social skills training to improve behaviour and communication. Several different treatment suites have been developed, including Applied Behavioural Analysis (ABA), Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH), and sensory integration. Specialized therapies include speech, occupational, and physical therapy. There is no standard medical treatment for autism, but problematic behaviours and symptoms are sometimes treated with such pharmaceuticals such as antidepressants, antipsychotics, anticonvulsants and methylphenidate. However, no disease-modifying treatment exists.